11-134283772-C-A

Position:

• chr11-134283772-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001080407.3(GLB1L3):​c.563C>A​(p.Thr188Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GLB1L3 NM_001080407.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.39

Genes affected

GLB1L3 (HGNC:25147): (galactosidase beta 1 like 3) Predicted to enable beta-galactosidase activity. Predicted to be involved in carbohydrate metabolic process. Predicted to be active in vacuole. [provided by Alliance of Genome Resources, Apr 2022]

GLB1L3 (HGNC:):

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLB1L3	NM_001080407.3	c.563C>A	p.Thr188Lys	missense_variant	6/20	ENST00000431683.7	NP_001073876.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLB1L3	ENST00000431683.7	c.563C>A	p.Thr188Lys	missense_variant	6/20	5	NM_001080407.3	ENSP00000396615.2
GLB1L3	ENST00000389887.9	c.563C>A	p.Thr188Lys	missense_variant	6/10	1		ENSP00000374537.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.563C>A (p.T188K) alteration is located in exon 6 (coding exon 6) of the GLB1L3 gene. This alteration results from a C to A substitution at nucleotide position 563, causing the threonine (T) at amino acid position 188 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.80	.;D
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.64	T;T
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.5	M;M
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.3	D;D
REVEL	Pathogenic	0.85
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.97	D;P
Vest4		0.96
MutPred		0.82		Gain of ubiquitination at T188 (P = 0.0408);Gain of ubiquitination at T188 (P = 0.0408);
MVP		0.61
MPC		0.28
ClinPred		0.95	D
GERP RS		3.9
Varity_R		0.71
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-134153666;